声动力疗法通过p38MAPK/SRF通路抑制血管平滑肌细胞表型转化和动脉内膜增生

Sonodynamic therapy inhibits vascular smooth muscle cell phenotypic switching and neointimal hyperplasia through p38 MAPK/SRF pathway

目的研究声动力疗法(SDT)对血管损伤后血管平滑肌细胞(VSMCs)表型转化和内膜增生的作用及机制。方法通过球囊损伤建立大鼠颈动脉内膜增生模型。应用HE染色、免疫组化、Western blot等方法观察加入p38MAPK抑制剂前后SDT对内膜增生和VSMCs不同表型标记物表达的影响。结果与对照组相比,SDT处理后动脉新生内膜与中膜比值明显减少,免疫组化染色显示PCNA阳性细胞百分比显著减少,Western blot显示收缩型VSMCs标记物SM22α和α-SMA以及磷酸化p38 MAPK和血清应答因子(SRF)表达增加。应用p38MAPK抑制剂逆转了SDT对VSMC表型转化和内膜增生的抑制。结论SDT通过p38MAPK/SRF通路抑制VSMC表型转化和内膜增生。

Objective To study the effect of SDT on VSMC phenotypic switching and neointimal hyperplasia in vivo after vascular injury. Methods Rat carotid neointimal hyperplasia model was established by balloon injury. HE staining, immunohistochemistry and Western blot were used to observe the effect of SDT on the neointimal hyperplasia and the expression of the markers of different phenotype of VSMCs before and after the administration of p38 MAPK inhibitor. Results Compared with the control group, the artery neointima-to-media area ratio was significantly reduced in SDT-treated rats. Immunohistochemical staining showed that the percentage of proliferating cell nuclear antigen-positive cells was significantly decreased in the injured arteries of SDT-treated rats. Western blot showed that SDT increased the expression of contractile markers smooth muscle 22α and α-smooth muscle actin, and the protein level of phosphor-p38 mitogen-activated protein kinase(p38 MAPK) and serum response factor(SRF). Pharmacological inhibition of p38 MAPK reversed the suppressive effects of SDT on VSMC phenotypic switching and neointimal hyperplasia. Conclusion SDT suppressed VSMC phenotypic switching and neointimal hyperplasia through p38 MAPK/SRF pathway.